The aims of this project are to evaluate the adaptation of the cardiovascular system to several stresses at rest and during exercise, to examine the neurologic control of the cardiovascular system to various stresses, and to evaluate the effects of various therapeutic regimens on the cardiovascular adaptation and on recovery from stresses. Stresses to be employed include acute and chronic hypertension (renal artery constriction), volume overload (arteriovenous fistula), chronic ethanol administration, thyrotoxicosis, aortic insufficiency and coronary artery constriction. Mongrel dogs will be chronically instrumented to measure left ventricular, aortic and left atrial pressure and their derivatives, aortic flow and left ventricular diameter. The animals will be studied at rest and various levels of graded exercise in 5 states - control, after beta-adrenergic blockade, after vagal blockade, after combined beta-adrenergic and vagal blockade and after digitalis. After suitable baseline data are obtained, the dogs will be exposed to a stress; as the dogs adapt to the stress the 5 interventions will be re-evaluated at regular intervals until ventricular function has changed significantly; then the stress will be removed, if possible, to examine recovery from chronic stress. Regional blood flow patterns will be determined using radioactive microspheres injected into the left atrium at rest, and during exercise both before and during the stress. Data from these studies should provide a better understanding of the cardiovascular adaptation to stress and provide a basis for better understanding of rational therapeutic interventions into the disease state.